The Atherosclerosis Risk in Communities Study (ARIC), funded under contract by NHLBI, is an on-going, prospective epidemiologic study conducted in four U.S. communities. ARIC is designed to investigate the etiology and natural history of atherosclerosis, the etiology of clinical atherosclerotic diseases, and variation in cardiovascular risk factors, medical care and disease by race, gender, location, and date. ARIC includes two parts: the Cohort Component and the Community Surveillance Component. The Cohort Component began in 1987, and each ARIC field center randomly selected and recruited a cohort sample of approximately 4,000 individuals aged 45-64 from a defined population in their community. A total of 15,792 participants received an extensive examination, including medical, social, and demographic data. These participants were reexamined every three years with the first screen (baseline) occurring in 1987-89, the second in 1990-92, the third in 1993-95, and the fourth and last exam was in 1996-98. Follow-up occurs yearly by telephone to maintain contact with participants and to assess health status of the cohort. The current study (funded in August 2004 as a grant under the direction of Dr. Eric Boerwinkel) began in early 2005 to re-examine a sample of the above-described cohort for various measures of cardiovascular disease including retinal microvasculature changes and arteriolosclerosis with the ultimate goals of identifying novel cellular, metabolic and genomic correlates of pathologic vascular changes and determining their impact on cardiovascular disease events. Retinal vasculature changes occuring over a decade's time (digitized retinal photographs were obtained in ARIC visit three) are be re-assessed with recently refined methodology and will be correlated with changes observed in large vessels to determine, for example, whether retinal arteriolosclerosis is a significant predictor of overt cardiovascular disease. In addition, cellular, metabolic, and genomic measures of monocyte and platelet activation and aggregation will be obtained from plasma and DNA, respectively, and analyzed in conjunction with the vascular findings from the retina and other non-ocular tissues.